Cardiovascular Physiology Autonomic Function Laboratory

The global focus of the Cardiovascular Physiology/Autonomic Function Laboratory is to examine the adaptive capacity of the circulation. Dr. Levine studies the effects of exercise training, bed rest deconditioning, spaceflight, high altitude, aging, and the effects of cardiovascular diseases such as heart failure. By using sophisticated tools to assess cardiovascular structure and function, Dr. Levine's research team brings "Olympic" and "space age" science to the solution of common clinical problems such as fainting, hypertension, or patients with shortness of breath. The exercise lab focuses on measuring how the cardio-respiratory system distributes oxygen from the environment to the muscles; it is one of the few labs in the world that can measure the limitations to exercise capacity at every step along the "oxygen cascade" including the lungs, heart and muscles. The lab uses invasive and non-invasive tools to assess cardiovascular structure and function, as well as circulatory control mechanisms.

Interests

The exercise component in preventing stiffening of the heart in individuals at high risk for future development of heart failure: Sedentary middle aged (ages 45-64) individuals are at high risk for future development of heart failure due to hypertension (high blood pressure). To date, no effective therapy for heart failure with preserved ejection fraction (HFpEF) has been found. Dr. Levine's lab believes prevention of heart stiffening is critical, and seeks to determine if exercise training in high risk individuals may improve the diastolic function of the heart and cardiac-vascular interactions, preventing further progression to overt heart failure. Dr. Levine's team is training 45 -64 year olds with left ventricular hypertrophy for one year with an exercise regimen of 4-5 days per week to see if cardiac and vascular compliance improves with vigorous exercise.

Novel Strategies to prevent obesity related abnormalities in diastolic function that may progress to heart failure with preserved ejection fraction (HFpEF):Dr. Levine's lab wants to determine whether 1 year of supervised exercise training in obese individuals at high risk for developing heart failure, incorporating high intensity interval training (HIIT) two to three times per week in conjunction with daily oral administration of omega-3 poly-unsaturated fatty acids will lead to reduction in visceral fat, regression of myocardial triglyceride levels and improvements in cardiac diastolic and vascular function.

The study of a more extreme form of heart stiffening as natural aging occurs, causing heart failure (HFpEF): This multi-factorial condition, also called “diastolic heart failure” is associated with several abnormalities in diastolic function including increased chamber stiffness and impaired relaxation, as well as impaired ventriculo-arterial coupling all of which also develop with advanced age. To date, there is no consensus on the key physiologic pathways that cause heart failure. Dr. Levine’s lab seeks to find strategies that can prevent heart failure from occurring.

Vigorous long term endurance sports and the increased risk for the development of atrial fibrillation in middle-aged adults: Several studies have reported an association between vigorous sports performed over a prolonged period of time and the development of atrial fibrillation by middle age. We are assessing changes that occur in the heart in response to long term triathlon training and evaluate the potential risk to develop this heart rhythm abnormality.

The comparison of pulsatile versus non-pulsatile Left Ventricular Assist Devices (LVAD): There are two different types of LVAD devices on the market today: those that pump blood continuously; and those that pump blood in a pulsatile fashion like the heart’s natural pumping action. Dr. Levine’s lab seeks to identify how these different types of LVAD’s affect the ability of the heart and nervous system to control blood pressure and blood flow to the brain, since they, may be sensed quite differently by the blood pressure control system.

Consequences of bed rest or space flight (deconditioning) on the heart and blood pressure regulation: Decreases in cardiac mass, and a fall in stroke volume due to several physiological factors can cause orthostatic intolerance. Dr. Levine’s lab seeks to identify these physiologic factors and explore treatments to reverse them or prevent deconditioning.


Current Projects

  • Prevention of Cardiovascular Stiffening with Aging and Hypertensive Heart Disease
  • Reduction of Cardiac Steatosis and Improvement of Diastolic Function by Modulating Metabolic Health in Obese Individuals
  • Hemodynamic response to exercise in HFpEF patients after upregulation of SERCA2a(funded by NIH – National Institutes of Health)
  • Determinants of Chronotropic Incompetence in Patients with Heart Failure and a Preserved Ejection Fraction (HFpEF)(funded by NIH – National Institutes of Health)
  • The Effect of Simulated Spaceflight on Intracranial Pressure
  • Is Vigorous Long term Endurance Sports a Risk Factor for the Development of Atrial Fibrillation in Middle–aged Adults?
  • Hemodynamics, autonomic neural function, and cerebral blood flow in patients with pulsatile and continuous flow left ventricular assist devices (unfunded)​

Publications

  1. Fujimoto N, Hastings JL, Bhella PS, Shibata S, Gandhi NK, Carrick-Ranson G, Palmer MD, Levine BD. Effect of Aging on Left Ventricular Compliance and Distensibility in Healthy Sedentary Humans. J Physiol. 2012 In press.
  2. Hastings JL, Levine BD. Syncope in the Athletic Patient. Prog Cardiovasc Dis. 2012 In press.
  3. Shibata S, Levine BD. Effect of exercise training on biologic vascular age in healthy seniors. Am J Physiol Heart Circ Physiol. 2012; Mar; 302(6):H1340-6.
  4. Bhella PS, Prasad A, Heinicke K, Hastings JL, Arbab-Zadeh A, Adams-Huet B, Pacini EL, Shibata S, Palmer MD, Newcomer BR, Levine BD. Eur J Heart Fail. 2011 Dec;13(12):1296-304.
  5. Shibata S, Hastings JL, Prasad A, Fu, Q, Bhella PS, Pacini E, Krainski F, Palmer MD, Zhang R, Levine BD. Congestive heart failure with preserved ejection fraction is associated with severely impaired dynamic Starling mechanism. J Appl Physiol. 2011; 110: 964–971.
  6. Fujimoto N, Prasad A, Hastings JL, Arbab-Zadeh A, Bhella PS, Shibata S, Palmer MD, Levine BD. Cardiovascular Effects of 1 Year of Progressive and Vigorous Exercise Training in Previously Sedentary Individuals Older Than 65 Years of Age. Circulation. 2010; 122: 1797-1805.
  7. Shibata S, Perhonen M, Levine BD. Supine cycling plus volume loading prevent cardiovascular deconditioning during bed rest. J Appl Physiol. 2010; 108: 1177–1186.
  8. Markham DW, Fu Q, Pacini E, Bhella PS, Minniefield N, Metzemaekers LF, Ridder D, Galbreath MM, Palmer MD, Shibata S, Zhang R, Bethea BT, Meyer DM, Patel PC, Drazner MH, Levine BD. Non-pulsatile left ventricular assist device (LVAD) patients have exaggerated hemodynamic and autonomic responses to head up tilt compared to pulsatile LVAD patients and controls. Circulation. 2009; I 20: S843.
  9. Prasad A, Hastings JL, Shibata S, Popovic ZB, Arbab-Zadeh A, Bhella PS, Okazaki K, Fu Q, Berk M, Palmer MD, Greenberg NL, Garcia MJ, Thomas JD, Levine, BD. Characterization of Static and Dynamic Left Ventricular Diastolic Function in Patients With Heart Failure With a Preserved Ejection Fraction. Circ Heart Fail; 2010; 3:617-626.
  10. Arbab-Zadeh A, Dijk E, Prasad A, Fu Q, Torres P, Zhang R, Thomas JD, Palmer MD, Levine, BD. Effect of Aging and Physical Activity on Left Ventricular Compliance. Circulation. 2004; 110:1799-1805.
  11. Levine BD, Zuckerman JH, Pawelczyk JA. Cardiac atrophy after bed-rest deconditioning: a nonneural mechanism for orthostatic intolerance. Circulation. 1997; 96:517–525.
  12. Buckey JC Jr., Lane LD, Levine BD, Watenpaugh DE, Wright SJ, Moore WE, Gaffney FA, Blomqvist, CG. Orthostatic intolerance after spaceflight. Journal of Applied Physiology. 1996; 81, 7–18.​​